Endothelial cells (ECs) adapt their metabolism to enable the growth of new blood vessels, but little is known how ECs regulate metabolism to adopt a quiescent state. Here, we show that the metabolite ...S-2-hydroxyglutarate (S-2HG) plays a crucial role in the regulation of endothelial quiescence. We find that S-2HG is produced in ECs after activation of the transcription factor forkhead box O1 (FOXO1), where it limits cell cycle progression, metabolic activity and vascular expansion. FOXO1 stimulates S-2HG production by inhibiting the mitochondrial enzyme 2-oxoglutarate dehydrogenase. This inhibition relies on branched-chain amino acid catabolites such as 3-methyl-2-oxovalerate, which increase in ECs with activated FOXO1. Treatment of ECs with 3-methyl-2-oxovalerate elicits S-2HG production and suppresses proliferation, causing vascular rarefaction in mice. Our findings identify a metabolic programme that promotes the acquisition of a quiescent endothelial state and highlight the role of metabolites as signalling molecules in the endothelium.
ABSTRACT
We use deep imaging from the Dark Energy Camera to explore the peripheral regions of nine globular clusters in the outer halo of the Milky Way. Apart from Whiting 1 and NGC 7492, which are ...projected against the Sagittarius stream, we see no evidence for adjacent stellar populations to indicate any of these clusters is associated with coherent tidal debris from a destroyed host dwarf. We also find no evidence for tidal tails around any of the clusters in our sample; however, both NGC 1904 and 6981 appear to possess outer envelopes. Motivated by a slew of recent Gaia-based discoveries, we compile a sample of clusters with robust detections of extra-tidal structure, and search for correlations with orbital properties. While we observe that clusters with tidal tails are typically on moderately or very eccentric orbits that are highly inclined to the Galactic plane and often retrograde, these are neither necessary nor sufficient conditions for the formation of extra-tidal structure. That many objects with tidal tails appear to be accreted leads us to speculate that this lack of consistency may stem from the inhomogeneous dynamical history of the Milky Way globular cluster system. Finally, we note that clusters with prominent stellar envelopes detected in ground-based imaging (such as NGC 1851 and 7089) are now all known from Gaia to possess long tidal tails – experimental confirmation that the presence of an extended envelope is indicative of tidal erosion.
Adsorbent mesoporous materials are highly efficient for the remediation of different compounds in environmental applications such as organic, inorganic, and gas molecules. These compounds are removed ...by the traditional adsorption process in batch assessments. In this review, we report the recent progress on the MCM-41-based mesoporous material syntheses and its strategic use as an adsorbent material for the removal of different pollutants. Also approached the main factors that affect its synthesis and the methods of functionalization most used to prepare the MCM-41-based functionalized mesoporous materials. On the other hand, the factors that affect the adsorption process were also investigated. In addition, it is possible to affirm that adsorption technology has attracted a lot of attention in the removal of environmental pollutants, mainly due to the fact that it is a technique that requires the use of few steps and equipment, easy operation, low cost, does not generate residues or by-products, eco-friendly, and high energy efficiency, which allow its wide application on the remediation processes.
Applications of MCM-41-based mesoporous materials. Display omitted
•Mesoporous materials are highly efficient for the remediation of different pollutants.•MCM-41 has been the most investigated mesoporous material of M41S family.•MCM-41-based mesoporous materials can be synthesized by a variety of synthetic routes.•MCM-41-based mesoporous arrays were widely applicated in the adsorption technology.
Summary
Background
“Exercise‐induced gastrointestinal syndrome” refers to disturbances of gastrointestinal integrity and function that are common features of strenuous exercise.
Aim
To systematically ...review the literature to establish the impact of acute exercise on markers of gastrointestinal integrity and function in healthy populations and those with chronic gastrointestinal conditions.
Methods
Search literature using five databases (PubMed, EBSCO, Web of Science, SPORTSdiscus, and Ovid Medline) to review publications that focused on the impact of acute exercise on markers of gastrointestinal injury, permeability, endotoxaemia, motility and malabsorption in healthy populations and populations with gastrointestinal diseases/disorders.
Results
As exercise intensity and duration increases, there is considerable evidence for increases in indices of intestinal injury, permeability and endotoxaemia, together with impairment of gastric emptying, slowing of small intestinal transit and malabsorption. The addition of heat stress and running mode appears to exacerbate these markers of gastrointestinal disturbance. Exercise stress of ≥2 hours at 60% VO2max appears to be the threshold whereby significant gastrointestinal perturbations manifest, irrespective of fitness status. Gastrointestinal symptoms, referable to upper‐ and lower‐gastrointestinal tract, are common and a limiting factor in prolonged strenuous exercise. While there is evidence for health benefits of moderate exercise in patients with inflammatory bowel disease or functional gastrointestinal disorders, the safety of more strenuous exercise has not been established.
Conclusions
Strenuous exercise has a major reversible impact on gastrointestinal integrity and function of healthy populations. The safety and health implications of prolonged strenuous exercise in patients with chronic gastrointestinal diseases/disorders, while hypothetically worrying, has not been elucidated and requires further investigation.
Linked ContentThis article is linked to Uno and Costa et al papers. To view these articles visit https://doi.org/10.1111/apt.14330 and https://doi.org/10.1111/apt.14358.
Abstract
Bgee is a database to retrieve and compare gene expression patterns in multiple animal species, produced by integrating multiple data types (RNA-Seq, Affymetrix, in situ hybridization, and ...EST data). It is based exclusively on curated healthy wild-type expression data (e.g., no gene knock-out, no treatment, no disease), to provide a comparable reference of normal gene expression. Curation includes very large datasets such as GTEx (re-annotation of samples as ‘healthy’ or not) as well as many small ones. Data are integrated and made comparable between species thanks to consistent data annotation and processing, and to calls of presence/absence of expression, along with expression scores. As a result, Bgee is capable of detecting the conditions of expression of any single gene, accommodating any data type and species. Bgee provides several tools for analyses, allowing, e.g., automated comparisons of gene expression patterns within and between species, retrieval of the prefered conditions of expression of any gene, or enrichment analyses of conditions with expression of sets of genes. Bgee release 14.1 includes 29 animal species, and is available at https://bgee.org/ and through its Bioconductor R package BgeeDB.
Mutations of the mitochondrial genome (mtDNA) underlie a substantial portion of mitochondrial disease burden. These disorders are currently incurable and effectively untreatable, with heterogeneous ...penetrance, presentation and prognosis. To address the lack of effective treatment for these disorders, we exploited a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue: the m.5024C>T tRNA
mouse. Through application of a programmable nuclease therapy approach, using systemically administered, mitochondrially targeted zinc-finger nucleases (mtZFN) delivered by adeno-associated virus, we induced specific elimination of mutant mtDNA across the heart, coupled to a reversion of molecular and biochemical phenotypes. These findings constitute proof of principle that mtDNA heteroplasmy correction using programmable nucleases could provide a therapeutic route for heteroplasmic mitochondrial diseases of diverse genetic origin.
Dominance by cyanobacteria hampers human use of lakes and reservoirs worldwide. Previous studies indicate that excessive nutrient loading and warmer conditions promote dominance by cyanobacteria, but ...evidence from global scale field data has so far been scarce. Our analysis, based on a study of 143 lakes along a latitudinal transect ranging from subarctic Europe to southern South America, shows that although warmer climates do not result in higher overall phytoplankton biomass, the percentage of the total phytoplankton biovolume attributable to cyanobacteria increases steeply with temperature. Our results also reveal that the percent cyanobacteria is greater in lakes with high rates of light absorption. This points to a positive feedback because restriction of light availability is often a consequence of high phytoplankton biovolume, which in turn may be driven by nutrient loading. Our results indicate a synergistic effect of nutrients and climate. The implications are that in a future warmer climate, nutrient concentrations may have to be reduced substantially from present values in many lakes if cyanobacterial dominance is to be controlled.
Radial expansion for spinning conformal blocks Costa, Miguel S.; Hansen, Tobias; Penedones, João ...
The journal of high energy physics,
07/2016, Letnik:
2016, Številka:
7
Journal Article
Recenzirano
Odprti dostop
A
bstract
This paper develops a method to compute any bosonic conformal block as a series expansion in the optimal radial coordinate introduced by Hogervorst and Rychkov. The method reduces to the ...known result when the external operators are all the same scalar operator, but it allows to compute conformal blocks for external operators with spin. Moreover, we explain how to write closed form recursion relations for the coefficients of the expansions. We study three examples of four point functions in detail: one vector and three scalars; two vectors and two scalars; two spin 2 tensors and two scalars. Finally, for the case of two external vectors, we also provide a more efficient way to generate the series expansion using the analytic structure of the blocks as a function of the scaling dimension of the exchanged operator.
We present high-resolution Magellan/MIKE spectroscopy of 42 red giant stars in seven stellar streams confirmed by the Southern Stellar Stream Spectroscopic Survey (S5): ATLAS, Aliqa Uma, Chenab, ...Elqui, Indus, Jhelum, and Phoenix. Abundances of 30 elements have been derived from over 10,000 individual line measurements or upper limits using photometric stellar parameters and a standard LTE analysis. This is currently the most extensive set of element abundances for stars in stellar streams. Three streams (ATLAS, Aliqa Uma, and Phoenix) are disrupted metal-poor globular clusters, although only weak evidence is seen for the light-element anticorrelations commonly observed in globular clusters. Four streams (Chenab, Elqui, Indus, and Jhelum) are disrupted dwarf galaxies, and their stars display abundance signatures that suggest progenitors with stellar masses ranging from 106 to 107 M . Extensive description is provided for the analysis methods, including the derivation of a new method for including the effect of stellar parameter correlations on each star's abundance and uncertainty. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.
Emerging evidence suggests that cancer cell metabolism can be regulated by cancer-associated fibroblasts (CAFs), but the mechanisms are poorly defined. Here we show that CAFs regulate malignant cell ...metabolism through pathways under the control of FAK. In breast and pancreatic cancer patients we find that low FAK expression, specifically in the stromal compartment, predicts reduced overall survival. In mice, depletion of FAK in a subpopulation of CAFs regulates paracrine signals that increase malignant cell glycolysis and tumour growth. Proteomic and phosphoproteomic analysis in our mouse model identifies metabolic alterations which are reflected at the transcriptomic level in patients with low stromal FAK. Mechanistically we demonstrate that FAK-depletion in CAFs increases chemokine production, which via CCR1/CCR2 on cancer cells, activate protein kinase A, leading to enhanced malignant cell glycolysis. Our data uncover mechanisms whereby stromal fibroblasts regulate cancer cell metabolism independent of genetic mutations in cancer cells.
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